Clinical Characteristics And Prognosis Of Limbic Encephalitis Associated With Different Subtypes Of Anti-Neuron Surface Antigen Antibody

Objective:To investigate the clinical characteristics and prognosis of different subtypes of anti-neuron surface antigen antibody-associated limbic encephalitis.Methods:Patients with limbic encephalitis associated with anti-neuron surface antigen antibodies diagnosed in Qilu Hospital of Shandong University from May 2015 to January 2019 were selected.To collect clinical data of patients,The recovery,hormone and antiepileptic drug maintenance time,recurrence and residual symptoms of the patients were followed up,and the factors affecting the prognosis were analyzed.Results:There were 52 cases of anti-LGI1 encephalitis,39 males and 13 females.The age of onset was 30 to 77 years old,the median age was 60 years old.None of them complicated with tumor.The first symptoms were seizures in 30 cases,memory loss in 15 cases,cognitive impairment in 3 cases,abnormal mental behavior in 1 case,headache in 1 case,motor disturbance in 1 case and decreased consciousness in 1 case.In the course of the disease,seizures in 48 cases(FBDS in 25 cases),35 cases of memory impairment,31 cases of cognitive impairment,20 cases of mental and behavioral abnormalities,13 cases of decreased consciousness,11 cases of motor disorders,9 cases of autonomic movement and 7 cases of speech disorders,4 cases of autonomic nervous dysfunction and 27 cases of sleep disorder.Serological examination showed that 14 cases were hypokalemia,38 cases were hyponatremia,35 cases were hypochloremia,serum potassium,sodium and chlorine were lower than normal level(p<0 01),43 cases were detected by ProGRP and 7 cases were increased.The pressure of CSF and CSF leukocytes were mostly normal,the contents of glucose,protein and immunoglobulin IgG in CSF were increased(p<0.01),CSF chloride ion decreased(p<0.01),and the oligoclonal bands of CSF were negative.The positive rate of serum autoimmune encephalitis antibody(96%)was higher than that of CSF(87.5%).MRI examination was abnormal in 47%of the brain,mainly in hippocampus,and abnormal hypermetabolism was found in 1 case by PET.86%of the patients had abnormal EEG,mainly slow wave and epileptic discharge,and 2 patients had 5 brush.Treatment:50 patients received first-line immunotherapy,regardless of the interval between onset and treatment,and the mRS score decreased by 1.5 points on average after treatment.45 patients were treated with antiepileptic drugs.Levetiracetam or levetiracetam combined with valproic acid was the main drug.Prognosis:46 patients were followed up for 2 to 45 months,7 cases recurred.Most of the patients stopped taking antiepileptic drugs within 6 months or so.At the last follow-up,the average mRS score of 46 patients was 0.5.seizures were still found in 6 cases,memory impairment in 21 cases and cognitive impairment in 2 cases.The prognosis of patients was generally good,and there was no correlation between prognosis and age,the interval from onset to treatment,serum or CSF antibody titer and serological examination.There were 13 cases of anti-GABAB receptor encephalitis,including 10 males and 3 females,aged 28 to 74 years,with a median age of 65 years.There were 7 cases of tumor,6 cases of small cell lung cancer and 1 case of lung adenocarcinoma.The first symptoms were seizures in 11 cases,memory loss in 1 case and headache in 1 case.In the course of the disease,there were 13 cases of seizures(FBDS in 1 case),12 cases of memory impairment,10 cases of cognitive impairment,7 cases of decreased consciousness,6 cases of mental and behavioral abnormalities,3 cases of autonomic movement,2 cases of speech disorder,2 cases of motor disorder,l case of autonomic nervous dysfunction and 8 cases of sleep disorder.Serological examination showed that electrolyte disturbance was rare,but the level of serum potassium ion was lower than the normal level(p<0.01).ProGRP was detected in 10 cases,6 cases were elevated,and the ProGRP level was higher than the normal level(p<0.01).The pressure of CSF was mostly normal,the leukocyte count of CSF increased in half of the patients.The levels of CSF glucose,CSF protein,and CSF immunoglobulin IgG were higher than the normal level(p<0.05).CSF oligoclonal band detected in 10 cases,4 cases were positive.The positive rate of serum autoimmune encephalitis antibody(100%)was higher than that of CSF(82%).The antibody titer decreased or turned negative in 2 patients,and the serum paraneoplastic antibody was positive in 2 patients.The brain MRI examination was abnormal in 67%of the patients,and the hippocampus was mainly involved.89%EEG was abnormal,mostly slow wave and epileptic discharge.Treatment:10 cases received first-line immunotherapy,regardless of whether combined with tumor immunotherapy or not,the mRS score was improved by 1.3 points on average after treatment.In 11 cases of antiepileptic treatment,levetiracetam or levetiracetam combined with valproic acid was the main drug.Prognosis:11 patients were followed up for 3 to 31 months,6 cases died(4 cases of tumor),1 case recurred.The course of treatment of hormones and antiepileptic drugs was about 6 months.The average mRS score of 5 existing patients was 1 at the last follow-up.2 cases had memory impairment and 1 case still had seizures.There was no significant difference in mortality between patients with and without tumor(p=0.242),and there was no significant correlation between prognosis and age,interval from onset to treatment,serum or CSF antibody titer and serological examination.There were 2 cases of anti-AMPA receptor encephalitis,including 1 adult with anti-AMPA type 2 receptor encephalitis and 1 child with anti-AMPA type 1 receptor encephalitis.All of them were male,and the age of onset was 2 years old and 26 years old.Adult patients with B2 thymoma and myasthenia gravis.First symptoms:Adults have memory loss and children have seizures.In the course of the disease,seizures in 2 cases.The adult patients had abnormal mental behavior and the children had obvious sleepiness.Serological examination:The electrolytes were normal and none of ProGRP was detected.The CSF cytology white blood cell count and CSF protein content in adult patients was higher than normal;there was no abnormality in CSF examination and CSF oligoclonal band negative.Adult patients with serum and CSF autoimmune encephalitis antibodies were positive,serum anti-AChR antibody positive;children with positive serum antibodies,CSF negative.Adult patients with MRI were involved in bilateral hippocampus,and the children had no abnormal MRI.EEG in the child has an epileptiform discharge and turns to normal after immunotherapy.The children responded well to immunotherapy,followed up for 38 months,no residual symptoms;adult patients with poor first-line immunotherapy response,second-line immunotherapy symptoms were not improved,recurrence at 3 months,followed up for 9 months,the last follow-up mRS score was 5.The levels of serum sodium and chloride ion in anti-LGI1 encephalitis were lower than those in the other two subtypes(p<0.05),the level of chloride ion in CSF was lower than that in the other two subtypes(p<0.001).The positive rate of anti-GABAB receptor encephalitis:the positive rate of CSF oligoclonal band was significantly higher than that of the other two types of encephalitis(p<0.01).The level of ProGRP was significantly higher than that of anti-LGI1 encephalitis(p<0.01).The serum ProGRP level of tumor patients was significantly higher than that of non-tumor patients(p<0.01),and the prognosis of tumor patients was worse than that of non-tumor patients(p<0.01).The prognostic factors were CSF immunoglobulin IgM content(r=0.447,p<0.01)and mRS score on admission(r=0.419,p<0.05).Conclusions:The onset age of patients with anti-neuron surface antigen antibody-associated limbic encephalitis is more than 50 years old,most of them are males,with limbic system symptoms as the core manifestation,and sleep disorders are common.The positive rate of autoantibody in serum of patients with autoimmune encephalitis was higher than that of CSF.The titer of autoantibody decreased or turned negative with the remission of the disease.The positive rate of imaging examination was low,and the lesion mainly involved the hippocampus.Slow wave and epileptic discharge were the main types of EEG.Anti-LGI1 Encephalitis is characterized by the decrease of FBDS,hyponatremia,low blood chlorine and CSF chloride ion,and there is no tumor.AntiLGI1 Encephalitis has a good response to immunotherapy and a good prognosis.AntiGABAB receptor encephalitis is characterized by elevated ProGRP and positive CSF oligoclonal band,which is often complicated with small cell lung cancer,anti-GABAB receptor encephalitis immunotherapy is effective,the mortality rate is high,and the prognosis is different among individuals.Anti-AMPA receptor encephalitis is rare and can be complicated with thymoma.The response of anti-AMPA2 receptor encephalitis to immunotherapy is poor and the prognosis is poor,and the immunotherapy response of anti-AMPA2 receptor encephalitis is good,the clinical process is reversible and the prognosis is good.Immunotherapy of marginal encephalitis associated with anti-neuron surface antigen antibody is effective.Methylprednisolone combined with intravenous immunoglobulin is the main scheme,and levetiracetam or levetiracetam combined with valproic acid is the main antiepileptic drug.Simple antiepileptic drugs did not control seizures well,and the hormone maintenance time was about 6 months,and the maintenance time of antiepileptic drugs was less than 6 months.The prognosis of patients with tumor was poor,and the prognosis was related to the content of CSF immunoglobulin IgM and the severity of admi ssion.These diseases can have recurrence,some patients left memory disorders and seizures.